BGT-DTDS for Dopamine Transporter Deficiency Syndrome (DTDS) and Parkinson’s Disease

Dopamine Transporter Deficiency Syndrome (DTDS)

Disease Characteristics: DTDS is a rare, autosomal recessive childhood neurological disorder with significant disease burden, characterised by a severe parkinsonian movement disorder. DTDS results from biallelic mutations in the SLC6A3 which encodes the dopamine transporter (“DAT”), a key protein regulating dopaminergic signalling. Dopamine re-uptake by DAT is the principal mechanism by which dopamine is removed and recycled from synapses. Mutations in SLC6A3 result in DAT dysfunction and major dysregulation of dopamine neurotransmission, leading to hyperkinetic movement disorders in the early stages of the disease, and then evolution of parkinsonism-like features (slowing of voluntary movements, loss of facial expression, tremor, stiffness) and eye movement disorders such as oculogyric crises. The disease is often fatal in childhood to teenage years due to unexplained death in sleep or respiratory failure.

Unmet Need: There are currently no disease-modifying treatments or approved therapies for DTDS, and patients derive little clinical benefit from available symptom control medications.

Epidemiology: The disease is currently poorly diagnosed, due to symptoms similarity with other movement disorders including cerebral palsy, and the number of patients with the condition is unknown.